Navigation Links
Jefferson researchers unlock key to personalized cancer medicine using tumor metabolism
Date:4/15/2011

PHILADELPHIAIdentifying gene mutations in cancer patients to predict clinical outcome has been the cornerstone of cancer research for nearly three decades, but now researchers at the Kimmel Cancer Center at Jefferson have invented a new approach that instead links cancer cell metabolism with poor clinical outcome. This approach can now be applied to virtually any type of human cancer cell.

The researchers demonstrate that recurrence, metastasis, and poor clinical outcome in breast cancer patients can be identified by simply gene profiling cancer cells that are using ketones and lactate as a food supply.

These findings are reported in the April 15th online issue of Cell Cycle. The investigators are calling this new approach to personalized cancer medicine "Metabolo-Genomics."

High-energy metabolites have long been suspected to "fuel" aggressive tumor cell behavior. The researchers used this premise to generate a gene expression signature from genetically identical cancer cells, but one cell group was fed a diet of high-energy metabolites. These lactate- and ketone-induced "gene signatures" then predicted recurrence, metastasis, and poor survival.

So, it appears that what cancer cells are eating determines clinical outcome, not necessarily new gene mutations.

Michael P. Lisanti, M.D., Ph.D., Professor and Chair of Stem Cell Biology & Regenerative Medicine at Jefferson Medical College of Thomas Jefferson University and a member of the Kimmel Cancer Center at Jefferson, together with other researchers, found that treatment of human breast cancer cells with high-energy metabolites increases the expression of genes associated with normal stem cells, including genes upregulated in embryonic and neural stem cells.

What's more, lactate and ketones were found to promote the growth of normal stem cells, which has critical applications for stem cell transplantation and for a host of different human diseases. It appears that these metabolites increase "stemness" in cancer cells, which drives poorer outcomes.

"Tumors that are using the body's own nutrients (lactate and ketones) as "fuel" have a poorer outcome for patient survival, a behavior that now can be used to predict if a patient is at a high-risk for recurrence or metastasis," Dr. Lisanti said. "This is getting to the heart of personalized cancer medicine. Now, we have identified a panel of biomarkers that directly links cancer metabolism with targeted cancer therapy."

These findings suggest, according to the authors, that high-risk cancer patients (those whose cancer cells use high-energy metabolites) can be treated with new therapeutics that target oxidative mitochondrial metabolism, such as the antioxidant metformin, a drug that is also used to treat diabetes.

"Knowing the gene signatures of patients whose cancer cells are "eating" these metabolites (lactate and ketones) for fuel is a pivotal piece of new information that we can use to diagnose and treat cancer patients," said Martinez-Outschoorn, M.D., of the department of Medical Oncology at Thomas Jefferson University, and the lead author of the paper. "It's not just that we know those patients will have poor survival; we know that those patients are using mitochondrial metabolism, which is the type of energy metabolism that we should be targeting with new anti-cancer drugs."

The researchers propose that this new approach to diagnosis and subsequent treatment be called "Metabolo-Genomics" since it incorporates both cell metabolism and gene transcriptional profiling. This strategy could now be used to direct which patients receive a particular "tailored" anti-metabolic therapy.

Genetic markers, like expression of the mutationally activated HER2 gene, provide biomarkers that can be used to identify breast cancer patients at high-risk for recurrence or metastasis, and to modify their subsequent treatment with targeted therapies (i.e., herceptin, a drug used in aggressive breast cancers). But with "Metabolo-Genomics," it is now about using "global" cancer cell metabolism for these predictions.

"Just by feeding cancer cells a particular energy-rich diet, it changes their character, without introducing mutations or altering their genetic profile," Dr. Lisanti said. "We've only fed them high energy nutrients that help them to use their mitochondria, and this changes their transcriptional profile. It's a new biomarker for "lethal" cancers that we can now treat with the right drugs, such as the anti-oxidant metformin."

Dr. Lisanti and his colleagues believe that tumor metabolism is the new big picture for understanding how cancers undergo recurrence and metastasis.


'/>"/>

Contact: Steve Graff
stephen.graff@jefferson.edu
215-955-5291
Thomas Jefferson University
Source:Eurekalert

Related biology news :

1. Jefferson scientists deliver toxic genes to effectively kill pancreatic cancer cells
2. Jefferson Department of Surgery announces new pancreas tumor registry
3. Jefferson scientists discover a key protein regulator of inflammation and cell death
4. Jefferson researcher awarded Landenberger Foundation grant for ALS research
5. Jefferson receives $1.7 million grant to study stem cells in intervertebral discs of the spine
6. US Department of State names UCR entomologist a Jefferson Science Fellow
7. Jefferson scientists identify a new protein involved in longevity
8. Jefferson receives $3 million NIH grant to study molecular and genetic mechanisms in platelets
9. Jefferson researchers receive W.W. Smith Charitable Trust
10. Jefferson researchers provide genetic evidence that antioxidants can help treat cancer
11. Nature study: Jefferson researchers unravel proteins elusive role in embryo and disease development
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/9/2016)... Aware, Inc. (NASDAQ: AWRE ), a leading supplier ... fourth quarter and year ended December 31, 2015.  ... of 2015 was $6.9 million, an increase of 61% compared to ... the fourth quarter of 2015 was $2.6 million compared to $0.2 ... --> --> Higher revenue and operating income in ...
(Date:2/8/2016)... Czech Republic , February 8, 2016 /PRNewswire/ ... EU-regulated global payment platform which presents innovation for ... Biometrics Authentication feature called VoiceKey. --> ... platform which presents innovation for clients, comfort and ... called VoiceKey. --> Worldcore ...
(Date:2/4/2016)... 4, 2016 The field of Human ... the most popular hubs of the biotechnology industry. ... huge studies of human microbiota, have garnered a ... the microbiome space has literally exploded in terms ... This report focuses on biomedical aspects of research, ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... , Feb. 11, 2016  Spectra BioPharma Selling Solutions ... that provides biopharma companies the experience, expertise, operational ... deploy outsourced sales teams. Created in concert with ... both the strategic and tactical needs of its ... solutions through both personal and non-personal promotion. ...
(Date:2/11/2016)... BEACH, Florida , February 11, 2016 /PRNewswire/ ... PositiveID Corporation ("PositiveID" or "Company") (OTCQB: PSID), ... diagnostics, announced today that its Thermomedics subsidiary, which ... progress on its growth plan in January 2016, ... products distributors, increasing sequential monthly sales growth, and ...
(Date:2/11/2016)... ... February 11, 2016 , ... ... new stem cell treatment clinic in Quito, Ecuador. The new facility will provide ... applications to patients from around the world. , The new GSCG clinic ...
(Date:2/10/2016)... LOUISVILLE, Ky. , Feb. 10, 2016 ... company utilizing its proprietary NeXosome® technology for early ... presentation of its most recent study by Dr. ... Hospital at the Society for Maternal Fetal Medicine,s (SMFM) ... , GA, February 1-6 th , 2016.  The presentation ...
Breaking Biology Technology: